JP2013526544A5 - - Google Patents

Claims (19)

formula:
(Where
W is selected from O, S, CR ₄ , N or NR ₄ ;
Y is selected from O, S, CR ₄ , N or NR ₄ ;
Z is selected from O, S, N, NR ₄ or CR ₄ ;
X ₁ is carbonyl,;
X ₂ is an N R _4;
X ₃ is an S O _2;
X ₄ is selected from carbonyl, thiocarbonyl, S, SO, SO ₂ , CH ₂ , aryl optionally substituted with CR ₂ R ₃ , R ₄ , heteroaryl optionally substituted with R ₄ ;
R is optionally substituted heteroaryl with one or more R _4;
R ₁ is one or more R ₄ optionally substituted with a CR ₂ R ₃ aryl, one or more CR optionally substituted with R _{4 2} R ₃ heteroaryl, optionally with one or more R ₄ Substituted heteroaryl, aryl optionally substituted with one or more R ₄ , C _3-10 cycloalkyl, C containing C, O, S or N optionally substituted with one or more R ₄ Selected from _3-8 membered rings;
R ₂ is H, halogen, CF ₃ , C _1-6 alkyl, C _3-10 cycloalkyl, C _3-8 containing C, O, S or N, optionally substituted with one or more R ₄ Selected from member rings ;
R ₃ is H, halogen, CF ₃ , C _1-6 alkyl, C _3-10 cycloalkyl, C _3-8 containing C, O, S or N, optionally substituted with one or more R ₄ Selected from member rings ;
R ₄ is H, OH, NR ₂ R ₃ , halogen, C _1-6 alkyl, C _3-10 cycloalkyl, CN, CONR ₁ R ₂ , SO ₂ NR ₁ R ₂ , OC _1-6 alkyl, alkoxy, Selected from CF ₃ ;
R ₅ is H, OH, NR ₁ R ₂ , halogen, C _1-6 alkyl, C _3-10 cycloalkyl, CN, CONR ₁ R ₂ , SO ₂ NR ₁ R ₂ , OC _1-6 alkyl, CF, Selected from CF ₂ , CF ₃ , C _1-6 alkyl-hydroxy;
n is 0-6)
Or a pharmaceutically acceptable salt or pharmaceutically acceptable derivative thereof. W is N, Y is C or N, Z is S, the compounds according to claim 1. W or at least one Y is N, Z is C or O, A compound according to claim 1. R is pyridine , X ₂ is NH , X ₄ is C H ₂ ; R ₁ is benzyl optionally substituted with one or more R ₄ , and R ₄ is H or methyl. 3. A compound according to claim 2 . R is pyridine, X ₁ is carbonyl, X ₂ is NH, X ₃ is SO ₂ , X ₄ is C; R ₁ is optionally substituted with one or more R _{4 4.} A compound according to claim 3 which is benzyl and R4 is H or methyl. R is pyridine, X ₂ is NH, n = 0, R ₁ is phenyl optionally substituted with one or more R _4, A compound according to claim 2. R is Ri heteroaryl or pyridine der, and a X ₂ is NH / or optionally, and / or an optionally X ₄ is H, n is 0 or 1, A compound according to claim 1. The compound has the following formula:
Compound, or a pharmaceutically acceptable salt or pharmaceutically acceptable derivative thereof A compound according to claim 1. The compound has the following formula:
Compound, or a pharmaceutically acceptable salt or pharmaceutically acceptable derivative thereof A compound according to claim 1. The compound has the following formula:
2. The compound according to claim 1, wherein the compound is: The compound of claim 1 for use in (i) a method of treating a mammalian neurotransmission dysfunction or other pathology associated with mGluR4 activity, or (ii) a method of enhancing mGluR4 activity in a subject . Or a pharmaceutically acceptable salt or pharmaceutically acceptable derivative thereof. Subject Ri mammal der, and / or optionally mammal Ru humans der, the compounds for use according to claim 11. Said dysfunction is Parkinson's disease, schizophrenia, psychosis, `` schizophrenia-region '' disorder, depression, bipolar disorder, cognitive impairment, delirium, amnesia disorder, anxiety disorder, attention disorder, obesity, eating disorder, Or NMDA receptor related disorders , anxiety, motor activity after alcohol consumption, nerve fate restraint and neuronal survival, epilepsy, or certain cancers including medulloblastoma, including inflammation and diabetes, including multiple sclerosis metabolic disorders, and mGluR4 receptor is any of taste potentiators associated with glutamatergic dysfunction and diseases involving compounds for use according to claim 11. 12. The compound according to claim 11 , wherein the dysfunction is Parkinson's disease. A pharmaceutical composition comprising the compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt or pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier. Mammalian mGluR4 receptor activity comprising combining a compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt or pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier. A method for producing a medicament for enhancing the resistance. The compound is in a dosage and amount effective to treat a neurotransmitter dysfunction in a mammal,
(i) the drug has a known side effect of increasing the metabotropic glutamate receptor activity or,
(ii) drugs known to treat disorders associated with increasing metabotropic glutamate receptor activity, or
(iii) Drugs known to treat neurotransmitter dysfunction or other diseases associated with enhanced mGluR4 activity
12. A compound for use according to claim 11 administered in combination with one or more of: Co-administration is substantially simultaneously and / or optionally sequentially and / or optionally the mammal is a human and / or optionally the dysfunction is Parkinson's disease, schizophrenia, psychosis, “schizophrenia” 18. The `` disease-region '' disorder, depression, bipolar disorder, cognitive impairment, delirium, amnestic disorder, anxiety disorder, attention disorder, obesity, eating disorder, or NMDA receptor related disorder Compound for use in. 12. A compound for use according to claim 11 as a taste enhancer.